 - Known central nervous system CNS disease except for treated brain metastasis; treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging MRI or CT stable dose of anticonvulsants are allowed; treatment for brain metastases may include whole brain radiotherapy WBRT, radiosurgery RS; gamma knife, linear accelerator LINAC, or equivalent or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded 