- Have active central nervous system disease, including CNS involvement by malignancy or evidence of blood in the CNS such as subdural hematoma. If a subject has any neurological abnormality on examination, a baseline brain MRI is required to exclude structural disease and/or intracranial bleeding. Patients with clinically significant intracranial lesions should be excluded. Patients with common age-related changes that are not clinically significant (i.e. moderate small vessel ischemic changes) do not need to be excluded.