Inclusion Criteria:

• Patients with cytologically or histologically confirmed NSCLC.
• Patient with brain metastasis not amenable to surgery or radiosurgery with curative intent
• At least one brain measurable lesion using RECIST criteria
• ECOG Performance Status ≤2
• No prior chemotherapy for this cancer
• Prior surgery is allowed provided there is a relapse or progression after the procedure.
• Adequate organ function including the following: Adequate bone marrow reserve: absolute neutrophil count (ANC) superior or equal to 1.5 X109/L, platelets superior or equal to 100 X 109/L, and hemoglobin superior or equal to 9 g/dL; Hepatic: bilirubin <1.5 times the upper limit of normal (ULN), alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) <3xULN (or <5xULN with liver metastases); Renal: Calculated creatinine clearance (CrCl) superior or equal to 45mL/min based on the standard Cockroft and Gault formula
• Signed informed consent document from the patient
• Patient must be at least 18 years of age.
• Estimated life expectancy of at least 12 weeks.
• Effective contraception (men and women) for and during the 6 months following the end of treatment

Exclusion Criteria:

• Symptomatic brain metastasis
• Have received prior radiotherapy for brain metastasis
• Unable or unwilling to take folic acid, vitamin B12 supplementation or dexamethasone (or equivalent corticosteroid); or any other inability to comply with protocol or study related procedures.
• A prior malignancy other than NSCLC, except carcinoma in situ of the cervix or non-melanoma skin cancer, adequately treated low grade [Gleason score <6] localized prostate cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
• Serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram (ECG) indicative of cardiac disease) that, in the opinion of the investigator, would compromise the safety of the patient and his/her ability to complete study.
• Inability to discontinue administration of aspirin at a dose >1.3g/day or other non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam).
• Presence of fluid accumulations in third spaces, e.g., ascite or pleural effusion, which can be detected clinically (during physical examination), and which cannot be adequately controlled by drainage or other procedures prior to inclusion in the study.
• Peripheral neuropathy > CTC Grade 2
• Patient compliance or geographic distance precluding adequate follow up.