Selenium WebDriver allows you to automate anything you might do with all supported web browsers. If SAP CRM is a web application (and not a ActiveX document, Java Applet, etc. in an HTML OBJECT) then you should be able to automate your user actions using Selenium WebDriver.
Selenium does support IE11. I'm using it with IE11 right now.
Can you test usability manually? If you have a purely web based tests which has a measurable way to say an application is usable then you can automate that with Selenium. If you can manually manipulate a web application and the verification of usability is not measurable then Selenium isn't going to help you. You might be able to do something like test it manually, create a baseline of what the screen looks like then use a tool like Viff (visual diff) to test if the UI has changed. If the UI changes then you need to manually confirm the new layout is usable then create a new baseline.
Uploading and downloading of files is possible using desktop application tools. Selenium would do the browser manipulation but when the upload/download dialogs open control is passed to the desktop and you need a tool like AutoIt (or the Java Robot class) to automate the desktop interaction. Selenium is contained within the browser. We don't want the browser to be able to interact with your file system. If a browser did allow this, I'd be able to write a virus, download it to your browser when you visit my website and transfer files from your computer. This is a huge security no-no so Selenium alone cannot do it.
Is SAP UI5 is a desktop application then you are going to need to use a desktop application automation tool like AutoIt. I can use Java, the Selenium libraries and the AutoIt tool. The Java code would then use Selenium for web browser automation and AutoIt for automating things outside the browser.