Phase I Study of Temozolomide, Valproic Acid and Radiation Therapy in Patients With Brain Metastases

Inclusion Criteria:

* Patients must have cytologically/histologically documented solid tumor malignancies
* Age \> 18 years old
* Patients must be candidates to receive WBR for unresectable brain metastases
* Patients must have ECOG performance status 0-2
* Patients must be able to give informed consent and able to follow guidelines given in the study
* Neurologic Function Status 0,1, or 2
* The patient has no major impairment of hematological function, as defined by the following laboratory parameters: WBC \>3.0x10\^9/L; ANC \> 1.5 x 10\^9/L; Hgb \>9.0g/dL; PLT \>100x10\^9/L. Red blood cell transfusions and repeat evaluations for study entry are allowed
* Patients must have adequate renal and normal hepatic function (creatinine \< 1.5 x upper limit of normal (ULN), bilirubin and SGOT (AST), SGPT (ALT) within 1.5 x the upper institutional normal limits) obtained within 4 weeks prior to registration.
* All patients of reproductive potential must use an effective method of contraception during the study and six months following termination of treatment. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to female patients who are older than 50 years and have not had a menstrual cycle in more than one year).
* Women of childbearing age must have a negative pregnancy test
* Patients must have 10 mm or greater brain lesion on MRI scan performed within 4 weeks of enrollment

Exclusion Criteria:

* Prior whole brain radiation
* More than 1 active malignancy which may potentially cause brain metastasis
* Patients on phenytoin, carbamazepine, phenobarbital, felbamate, meropenem, rifampin (Levetiracetam will be permitted)
* Patients with active or any history of seizure disorders
* Patients with uncontrolled nausea and vomiting
* Chemotherapy, radiotherapy, or hormonal therapy within 2 weeks prior to entering the study or have not recovered from prior treatment-related toxicities (grade 2 or less)
* Patients receiving any other investigational agents
* Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study entry.
* Leptomeningeal disease or hydrocephalous on MRI scan performed within 4 weeks of enrollment
* Pregnant and breast feeding women are excluded from the study because effects on the fetus are unknown and there may be a risk of increased fetal wastage.